3. 5-diaminopyrazine-2. 6-dicarboxylic acid derivatives as optical brightening agents in cosmetic fatty creams



United States Patent 3,291,315 3.S-DIAMINOPYRAZINE-Z.-DICARBGXYLIC ACID DERIVATIVES AS GPTICAL BRIGHTENING AGENTS IN COSMETIC FATTY CREAMS Anthony Fenwick Dagiish, Clieadle Hulme, England, Rodolphe Vonderwahl, Riehen, near Basel, witzerland, and George Arnold Tillotson, Hale, England, assiguors to J. R. Geigy A.-G., Basel, Switzerland No Drawing. Original application May 23, 1958, Ser. No. 737,215, new Patent No. 3,843,780, dated July Ill, 1962. Divided and this application Jan. 15, 1962, Ser. No. 168,868 Claims priority, application Switzerland, May 29, 1957, 46,700/57 6 Claims. (Cl. 167-90) This is a division of application Serial No. 737,215, filed May 23, 1958, now US. Patent No. 3,043,780.

The invention concerns a new process for the production in good yields of 3.2:5.6-bis-[(2'.4-dioxo-1.2.3'.4- tetrahydro) 1.4'-pyrimidino] pyrazines and the derivatives of 3.S-diaminopyrazine-Z.6-dicarboxylic acids obtained therefrom by direct or step-wise saponification of free carboxyl groups while possibly further modifying such groups by amidation.

The invention also concerns a process for the improvement of the appearance in daylight of more or less colourless or white carriers by incorporation therein of slight amounts of the 3.5-bis-(sec. amino)-pyrazine-2.6-dicarboxylic acid. amides obtained according to thenew production process which, in UV-containing light, fluoresce violet-blue, blue to green blue.

The invention also concerns capillary active dispersing and cleansing agents which are characterised by a content of 3.5-bis-(sec. amino) pyrazine 2.6 4 dicarboxylic acid amides.

Up to know only a few processes are known for the production of 3.2:5.6-bis-[(2.4-dioxo-1'.2.3.4'-tetrahydro)-l.4-pyrirnidino]-pyrazines which have been given the common name of bis-alloxazines. According to the literature these processes only give poor yields because of the side reactions which occur and because of the often troublesome purification of the crude products due to these side reactions. Thus for example, Bredereck et al. (Berichte der deutschen chemischen Gesellschaft, vol 86, page 845 (1953)) relate yields of at most 45% of the theoretical for the condensation of 2 molecules of 1.3-dimethyl-4.S-diaminb-uracil in mineral acid solution while splitting ofi ammonium salt, or in vol. 87, page 1268 (1954) give the same yields for the condensation of one molecule of 1.3 dimethyl4,5 diamino-uracil with one molecule of 1.3-dimethyl-alloxan. Also Timmis in the US. Patent No. 2,581,889 mentions yields of up to 63% of crude 3.2:5.6-bis-[( 1.3-dimethyl-2.4-dioxo-1.2.3.4'- tetrahydro)-1'.4'-pyrimidino]-pyrazine (also called 1.3.1. 3'-tetramethyl-bis-alloxazine) for the condensation of one molecule of 1.3-dimethyl-4-amino-S-nitroso-uracil with one mol of 1.3-dimethyl barbituric acid.

It has now been found that very good yields of 3.5-diaminopyrazine-Z.6-dicarboxylic acid derivatives are obtained if one mol of 1.3-disubstitutecl 4-amino-uracil is condensed with 1 mol of 1.3-disubstituted 4-amino-5- nitrosouracil while splitting oil one mol of water and one mol of ammonia to form the corresponding 3.2:5.6-bis- [2.4-dioxo-l'.2'.3'.4 tetrahydro) 1'.4' pyrimidino1- pyrazine and this compound is saponified by known methods either director in steps to form derivatives of 3.5-diaminopyrazine-Z.fi-dicarboxylic acid, possibly while modifying free carboxylic groups by amidation.

The good yields obtained in the process according to the present invention are chiefly due to the fact that the new condensation of 1.3-disubstituted 4-amino-uracils with 1.3-disubstituted 4-amino-5-nitroso-uracils to form 332M515 Patented Aug. 17, 1965 ice 3.2: 5.6-bis-[ (2'.4'-dioxo-l.2.3 .4'-tetrahydro-1'.4'-pyrim idinol-pyrazines, which is performed advantageously in polar organic solvents with an acid reaction and preferably in low fatty acids, in particular in glacial acetic acid, proceeds more uniformly than the known processes.

Good yields of up to of the theoretical of these valuable intermediate products are obtained and this in contrast to the syntheses mentioned even when the nitrogen atoms of the uracils are substituted by higher organic radicals as methyl groups. Also the 3.2:5.6-bis-[(2.4- dioxo-l'.2.3.4-tetrahydro) 1'.4'-pyrimidino] pyrazines variously substituted at the nitrogen atoms of the two tetrahydropyrimidine rings are obtainable in good yields according to the new process. That the starting materials used according to the present invention would condense so favourably was surprising in view of the yields obtained in the known processes according to Bredereck and Timmis in which similar starting materials are used.

The 1.3-disubstituted 4-aminoor 4-amino-4-nitrosouracils used according to the present invention can be symmetrically or unsymmetrically substituted at the nitrogen atom. As nitrogen substituents both hydrocarbon radicals and also substituted hydrocarbon radicals of the aliphatic, araliphatic, alicyclic, or aromatic series are used, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, hydroxyethyl, methoxyethyl, ethoxethyl, 'y-methoxyprop yl, benzyl, chlorobenzyl, methylbenzyl, cyclophenyl, methyl-cyclohexyl, phenyl, methylphenyl, chlorophe'nyl, methoxyphenyl groups and starting materials having the same or different substituents at the nitrogen atom can be condensed.

Saponification of 3.2:5.6-bis-[(2'.4'-dioxo-1.2'.3.4'- tetrahydro)-1.4-pyrimidino]-pyrazines in aqueous, alcoholic or organic/aqueous solution or suspension, with alkalies such as sodium or potassium hydroxide, leads to the corresponding 3.5-bis-(sec. amino)-pyrazine-2.6-dicarboxylio acid amides. Under'more vigorous conditions, for example in ethanolic potassium hydroxide, the 3.5-bis- (sec. amino)-pyrazir1e-2.6-dicarboxylic acid monoamides are formed. In these compounds the free carboxyl group can be converted with thionyl chloride into the carboxylic acid halide group. Aminolysis of this group leads to the acid amides. A technically particularly simple method of performing the amidation consists in dissolving the carboxylic acid and the amine to be introduced in a strong tertiary nitrogen base such as pyridine, homologous pyridines or triethylamines and then stirring in gradually the necessary amount of thionyl chloride or phosphorus trichloride or bromide in the cold. After removal of the nitrogen base by dilution with water or steam, the 3.5-diaminopyrazine-Z.6-dicarboxylic acid diamide is obtained direct. The free carbonyl group, possibly in the form of its salts, can also be esterified, for example in treating with dialkyl sulphates.

Other derivatives can be obtained in the aminolysis of the acid chloride group by using amines which contain different substituents from those originally at the nitrogen atom which was linked to the carbonyl group. In this way, in particular also aromatic and heterocyclic amine radicals can be introduced, for example phenylamino, methylphenylamine, chlorophenylamino, methoxyphenylamino, pyridyl (2) amino and morpholino groups. However, it is also possible to introdue hydroxyalkylamino groups in this way,for example the monoethanolarnide, diethanolamide, Z-hydroxypropylamide group, also aminoalkyl carboxylic acid, carboxylic acid ester and carboxylic acid amide groups. substituted urea groups, e.g. the monophenyl urea group can be introduced in this way.

However, also unsymmetrical amidated end products can be obtained by aminolysis of 3.2:5.6-bis-[ (2'.4'-dioxo Even urea and higher temperature with amines such as eg benzylamine, whereby only one dioxo-tetrahydropyrimidino ring is split, and then further hydrolysing with alkalies.

There are, thus, several methods by which it is possible to vary at will the substitution of the diamin'opyrazine dicarboxylic acid amides according to the desired intended use.

The following sequence illustrates the reactions described:

I II II carrier, are incorporated into the material to be brightened. By carriers are meant substances from the class of natural and synthetic polypeptides such as wool, silk, polyarnide fibres, polyurethane fibres; vinyl polymers such as polyvinyl chloride, polyacrylic acid esters, polystyrene,

polyethylenes, unsaturated polyesters; cellulose acylates such as cellulose acetates to cellulose triacetate; also cellulose nitrates, e.g. in the form of Zapon varnishes. The 3.5-di-(sec. amino)-pyraZine-2.6-dicarboxylic acid deriva- Both the intermediate steps of the Formulate HI to V as well as the end steps of the Formula IV are valuable intermediate products for the production of pharmaceutical active ingredients.

The derivatives of the 3.S-diaminopyrazine-Z.6-dicarboxylic acid fluoresce in UV-containing light more or less strongly depending on their composition. The 3.5- bis-(sec amino)-pyrazine-2.6-dicarboxylic acid amides of the general'Formula IV, wherein X represents an amide radical, in particular the radical of a primary amine are particularly valuable because of their violet-blue, blue to green-blue fluorescence.

In the above sequence of reactions, R R R R R R and R, can represent the same or different organic radicals which have no dyestuif character; R and R-; can represent in addition, hydrogen.

R R R R represent preferably aliphatic radicals such as alkyl and substituted alkyl groups, for example methyl, ethyl, n-propyl, n-butyl, hydroxyethyl, ,B-hydroxypropyl, methoxyethyl, ethoxyethyl groups, however, they may also possibly represent aralkyl and substituted aralkyl groups such as benzyl, methylbenzyl, chlorobenzyl, methoxybenzyl groups or cycloaliphatic radicals such as cyclohexyl, methyl-cyclohexyl groups. R and R can be hydrogen or the same as R in addition R can also be a heterocyclic radical, for example the Z-pyridyl radical or a divalent radical linking two pyrazine radicals, for example an alkylene or a diphenyl all-Lane radical; it can also represent a carbamyl radical, for example the phenyl carbamyl radical and thus X can also represent a urea radical or a ureido radical which may possibly be organically substituted. R and R together with the carbamide- N- atom can also represent a heterocyclic radical, for example a piperidino or a morpholino group.

Because of their fluoroescence in ultraviolet light and in daylight, the 3.5-di-(sec. amino)-pyrazine-2.6-dicarboxylic acid derivatives of the Formula IV wherein X represents an amine radical, in particular the radical of a primary amine, are suitable for improving the appearance of more or less colourless carriers by optically compensating the yellowing thereof by the violet-blue, blue to green-blue fluorescence. For this purpose, slight amounts thereof, for example amounts of 0.001 to 1% of the tives can also be used as additives to cosmetic preparations, for example in lipsticks and creams. They can also be incorporated into carbohydrates such as starches, or fats and waxes as well as parafiines.

An important application is for the improvement of the appearance of textile fibres at any stage of processing by treating them with aqueous liquors which contain emulsifying, capillary active substances in addition to the 3.S-diaminopyrazine-2.6-dicarboxylic acid amides. In particularly valuable compositions according to the present invention, the emulsifying agents also have cleansing proper ties. The capillary active substances can be used as such, or mixed with each other and also admixed with the usual additives (builders). Both the usual water soluble soaps and also synthetic, organic non-soap anionactive sulphated detergents can be used as cleansing agents. These washing agents can contain substances from the following classes for example:

(A) Anion active substances:

(1) Sodium, potassium and alkanol amine salts of higher fatty acids containing 8 to 18 carbon atoms in the hydrocarbon radical;

(2) Alkali metal and ammonium salts of monosulphuric acid esters of: fatty alcohols having 10 to 30 carbon atoms, glycerine monoesters of fatty acids having 8 to 18 carbon atoms, oxalkyl ethers of fatty alcohols and alkyl phenols having lipophilic hydrocarbon radicals, fatty acid alkanol amides having lipophilic hydrocarbon radicals, polyglycol ethers of fatty alcohols having 10 to 30 carbon atoms;

(3) Alkali metal and ammonium salts of sulphonic acids from: paraffines (mersolates), alkylbenzenes naphthols (dodecyl benzene sulphonates, isobutyl naphthol sulphonates, methyl dinaphthyl sulphonates), benzimidazols having a higher alkyl or alkenyl radical in the 2-position, N-phenyl-l.3.5- triazines having a lipophilic hydrocarbon radical of 12 to 18 carbon atoms, succinic acid esters of alkanols having 6 to 12 carbon atoms;

(4) Amide-like condensation products of higherfatty acids with: isethionic acid (Igepon A), taurine and N-methyl taurine (Igepon T) (B) Non-ionogenic substances:

(1) Polyglycol ethers of higher alkanols and higher fatty acids as well as of alkyl phenols having lipophilic hydrocarbon radicals;

(2) Polyglycol ethers of alkanol amides of higher fatty acids.

The following substances can be added either individually or combined to the washing agents mentioned above: The sodium or potassium salts of sulphuric acid, hydrochloric acid, carbonic acid, boric acid, silicic acids, phosphoric acids including those which, as ortho-phosphoric acids, have less water content; in addition, alkali metal perborates, percarbonate, persulphate; magnesium salts of meta-silicic acid; cellulose methyl or ethyl ethers, alkali metal salts of carboxymethyl cellulose (CMC), of ethylene diamine tetra-acetic acid and similar N-polyacetic acids which form complexes.

The 3.5-bis-(sec. amino)-pyrazine-2.6-dicarboxylic acid amides can be mixed with the aqueous washing liquors or with the washing and cleansing agents used in the production thereof. Particularly valuable are detergent compositions consisting essentially of water soluble, synthetic, organic anion active detergents selected from the group consisting of water soluble soaps and synthetic organic non-soap anion active sulphated detergents containing 0.001 to 5% by weight of a 3.5-diaminopyrazine- 2.6-dicarboxylic acid amide of the general formula:

N R1-NHT Rz-NH-OC \N wherein each of R R and R represents a member selected from the group consisting of lower alkyland phenyl-substituted methyl radicals and X represents an amino group. X can be primary amino or the radical of an organic primary or secondary amine. In the most valuable and therefore preferred compounds, X is the radical of a primary amine of the aliphatic, phenyl-substituted. lower aliphatic, alicyclic, mononuclear isocyclicaromatic. and heterocyclic series.

In the washing and cleansing agents according to the present invention which are intended for the treatment of textiles, the content of 3.5-bis-(sec. amino)-pyrazine- 2.6-dicarboxylic acid amides is advantageously 0.01 to 5%, calculated on the weight of the composition. On the other hand, if it is only desired to attain an improved appearance of the washing and cleansing agent itself, then a content of 0.001 to 0.5% is sufficient. Thus washing and cleansing agents according to the present invention are characterised by contents of 0.001 to 5% of 3.5-bis-(sec. amino)-pyrazine-2.6-dicarboxylic acid amide. These optical brightening agents can be incorporated in the washing and cleansing agents either EXAMPLE 1 3.5-bis-ethylaminopyrazine 2.6 dicarboxylic acid-bisethylamide of the formula:

212 parts of 1.3-diethyl-4-amino-5-nitroso-uracil and 183 parts of 1.3-diethyl-4-amino-uracil are dissolved in 750 parts of glacial acetic acid and the solution is refluxed for 3 hours while stirring. The grey-greenish solution is cooled, the precipitate formed is filtered off under suction, washed well with water and dried. 320 parts of 3225.6 -ibis [(1.-3-diethyl-2.4'-dioXo-1.2'.3'4- tetrahydro)-l.4-pyrimidino]-pyrazine are obtained as white crystals which melt at 2335-2345". This corresponds to a yield of 89% of the theoretical calculated on the l.3-diethyl-4-amino-S-nitroso-uracil used. An analytically pure preparation recrystallised from 75% acetic acid which melts at 235.5236 has the following elementary analysis:

Calculated for C H O N C=53.32%; H=5.59%; N 23.32%. 'Found: C 53.17%; H 5.61%; N=23. l=1%.

To saponify the 3.2:5.6-bis-[(1'.3-diethyl-2.4'-dioxo- 1'.2'.3'.4 tetrahydro) 1'.4 pyrimidino] pyrazine, 10 parts are refluxed for 2%. hours with 300 parts by volume of 1 N-caus-tic soda lye and 200 parts of ethanol. The precipitate which crystallises out on cooling is filtered off under suction, well washed and dried. 7.5 parts of 3.5-bis ethylamino pyrazine-2.6 dicarboxylic acid-bisethylamide (MP. 133-134") are obtained. An analyti-.

cally pure preparation recrystallised from ethanol, has the same melting point and the following elementary analysis:

Calculated for C H O N C=54.52%; H=7.84%; N=27.25%. Found: C=54.63%; Hl=8.00%; N: 27.21%.

On using thecorresponding amounts of 1.3-dipropyl-, 1.3-dibutyland 1.3-dimethyl-4-amino-uracil and of 1.3- dipropyl, 1.3-dibutyland 1.3-dimethyl-4-arnino-S-nitrosouracil, the following 3.2:5.6-bis-[(l.3-dialkyl-2'.4'- dioxo 1.2'.3.4 tetrahydro) 1'.4 pyrimidino] -pyraz alone or together with other optical brightening agents. ines are obtained in a similar manner:

Elementar anal sis, e c t Alkyl M.P., y y p r en deg.

C cald 0 found H cald H found N cald N found n-C H 150-151 55.66 55.70 6.23 6.52 11-0411, 115-116 60.59 60.32 7. 93 7. s2 16. 96 17.19 CH3 390 47. 4 47. 4 3. 95 4. 17 27. 6 27. 8

Particularly, in all roundtextile washing agents for house- By saponifyin'g these according to paragraph 2 of the hold use, the 3.5-bis-(sec. amino)-pyrazine-2.6-dicarboxylic acid amides, which are effective for certain more hyexample, the corresponding 3.S-bis-alkylaminopyrazine- 2.6-dicarboxylic acid-bis-alkylamides are obtained:

Elementary analysis, percent 1 The crystals contain crystal solvent.

V homogenised on. a set of mixing rollers at 130.

7 All these 3.S-bis-alkylaminopyrazine-Z.6-dicarboxylic acid-bis-alkylamides have a strong to very strong violetblue fluorescence depending on their composition. Because of this property they can be used as follows for improving the appearance of vinyl polymers:

(a) Polyvinyl chloride 0.07 part of 3.5-bis-methylaminopyrazine-2.6-dicarboxylic acid-bis-methylamide are added to 67 parts of polyvinyl chloride powder, 33 parts of dioctyl phthalate, 2 parts of di-n-butoxy tin dilaurate and 0.3 part of sodium penta-octyl tripolyphosphate, the mixture is Worked on a set of mixing rollers for 15 minutes at 160 and then drawn out into foils. The foils so produced have a more white appearance in daylight than those produced without a content of dialkylaminopyrazine dicarboxylic acid alkylamide. Opaque, white polyvinyl chloride foils of greatly improved appearance are obtained if 7 parts of titanium dioxide (Anatas) are added to the above mixture. The 3.5-bis-ethylamino-, 3.5-bis-propylaminoand 3.5- bis-butylamino-pyrazine 2.6 dicarboxylic acid-bis-ethyl, or -propylor -butylamides described in the above example can be used in the same manner with the same success.

(b) Polystyrene 100 parts of polystyrene powder are thoroughly mixed with 0003 part of 3.S-bis-methylaminopyrazine-2.6- dicarboxylic acid-bis-methylamide and the mixture is then The hard plates obtained are broken up and further worked up on an injection moulding machine or in presses. Objects having a much more white appearance in daylight than those produced without the addition of 2.5-bis-alkylaminopyrazine-Z.6-dicarboxylic acid-bis-alkylamides are obtained.

Opaque objects of improved appearance are obtained if 2 parts of titanium dioxide (Anatas) are added to the above mixture. The 3.5-bis-ethylamino-, 3.5-bis-propylaminoand 3.5-bis-bu-tylaminopyrazine-Z.6-dicarboxylic acid-bis-ethylamides, -bis-propylamides, or -bis-butylamides also described in the above example can be used in the same manner and with similar success.

(c) Polyethylene 0.05 part of 3.S-bis-propylaminopyrazine-2.6-dicarboxylic acid-bis-propylamide are mixed dry at room temperature with 100 parts of high pressure polyethylene in granulate form and the mixture is then worked into a tube in the extruder at l20-130. The object is considerably more white than that produced without brightening agent.

To produce opaque polyethylene, 0.1 part of 3.5-bispropylaminopyrazine 2.6 dicarboxylic acid bis-propylamide, 2 parts of titanium dioxide and 100 parts of polyethylene granulate are mixed and pressed at 120-130. A material is obtained in this way which has a considerably more white appearance in daylight than that produced without brightening agent. The 3.5-bis-ethylamino-, 3.5-bis methylaminopyrazine 2.6 dicarboxylic acid-bis-ethyl or -methyl amides described in the above example can be used in the same manner and with simiilar success.

(d) Polymethacrylic acid methylester 0.004 part of 3.5-bis-methylaminopyrazine-2.6-dicarboxylic acid-bis-methylamine are dissolved in 100 parts of monomeric methacrylic acid methyl ester, 0.1 part of lauroyl peroxide are added and the whole is poured into a form. The mixture is polymerised by heating for 24 hours at 60 and then tempered for 1 hour at 160. Because of its very beautiful blue-violet fluorescence, the glass clear resinous body obtained has a more brilliant appearance in daylight than non-brightened material.

If the brightening agent used is replaced by the same amount of the 3.5-bis-ethylaminoor 3.5-bis-propylaminm 8 pyrazine2.6-dicarboxylic acid-bis-ethylor -propyamides described in the above example, then similar beautifully brightened products are obtained.

(e) Acetyl cellulose 0.2 part of 3.S-bis-ethylarninopyrazine-Z.6-dicarboxylic acid-bis-ethylamide, 25 parts of diethyl phthalate and 75 parts of acetyl cellulose are dissolved in 900 parts of acetone. The solution is poured onto glass plates and, after evaporation of the acetone, a transparent film is obtained. In daylight this film seems to be much more brilliant than a corresponding film produced without the addition of brightening agent.

Opaque cellulose acetate films are obtained if 5 parts of titanium dioxide (Anatas) are added to the above mixture before it is poured onto the glass plates. The opaque films obtained are much more white in daylight than comparative samples produced without brightening agents.

(7) Creams A cold cream of dazzling white appearance is obtained if 0.1 part of 3.5-bis-methylaminopyrazine-2.6-dicarboxylic acid-bis-methylamide are dissolved in 25 parts of cetyl alcohol and this solution is mixed homogeneously in the mixing apparatus with 55 parts of paraflin oil, 10 parts of bleached beeswax and 10 parts of wool fat (anhydrous).

Similar creams are obtained if, instead of the brightening agent mentioned, the 3.5-bis-ethy1aminoor 3.5-bispropylamino-pyrazine-Z.6-dicarboxylic acid-bis-ethyl or -propyl amides mentioned in the above example are used.

Because of their favourable shade of fluorescence and their affinity, these 3.5-bis-alkylaminopyrazine-2.6-dicarboxylic acid-bis-alkylarnides are also suitable for the optical brightening of natural and synthetic polypeptide fibres according to the application methods described in Examples 2 and 3.

EXAMPLE 2 3-propylamino-S-ethylamino-pyrazine-2-carboxylic acid propylamide-6-carboxylic acid ethylamide of the formula:

42 parts of 1,3-diethyl-4-amino-5-nitroso-uracil and 42 parts of l.3-dipropyl-4-amino-uracil are dissolved in 150 parts of glacial acetic acid and the solution is refluxed for 3 hours while stirring. The pale brownish solution is cooled and diluted with water. The precipitate formed is filtered off under suction, Washed well with Water and dried. 70 parts of 3.2-[1'.3-diethyl-2'.4'-dioxo-1'.2.3'.4'- tetrahydro) 1'.4' pyrimidino]-5.6-[(1'.3-dipropyl-2.4'- dioxo 1.2'.3.4-tetrahydro) 1.4'-pyrimidino]-pyrazine are obtained in the form of white crystals which melt at 147.5-149". This corresponds to a yield of of the theoretical, calculated on the 1.3-diethyl-4-amino-5-nitroso-uracil used. An analytically pure product recrystallised from ethanol melts at 150-151 and has the following elementary analysis:

Calculated for C H N O C=55.66%; H=6.23%. Found: C=55.70%; H=6.52%.

To saponify the 3.2-[(1'.3'-diethyl-2.4-dioxo-1.2'.3'. 4'-tetnahydro) -.l.4'-pyrimidino] 5.6- (1C3 '-dipropyl-2.4- dioxo 1'.2'.3'.4' tetrahydro)-1'.4'-pyrimidino]-pyrazine, 1-0 parts are refluxed for 2 /2 hours with 300 parts by volume of 1 N-caustic soda lye and 200 parts of ethanol. The reaction mixture is cooled and then neutralised with diluted hydrochloric acid. The precipitate formed is filtered off under suction, washed and dried. 7.2 parts of 3 propylamino-S-ethylamino-pyrazine 2.6 dicarboxylic acid-Z-propylamide-6-ethylarnide are obtained. M.P. 91-92.

An analytically pure preparation recrystallised from ethanol has the following elementary analysis:

Calculated for C H N O C=57.12%; H=8.39%; N=24.98%. Found: C=57.14%; H=8.45%; N: 24.91%.

On condensing 4-amino-uracils with 4-amino-S-nitrosouracils which are differently alkyl substituted at the ring nitrogen atom, for example by using corresponding amounts of 1.3-dimethyl-, 1.3-diethyland 1.3-dipropyl- 4-amino-uracils and 1.3-dimethyl-, 1.3-diethyland 1.3- dipropyl- 4-amino-S-nitroso-uracils, the following unsymmetrical 3.2 5.6- 1'.3 '-dialkyl-2.4'-dioxo-1'.2.3.4-tetrahydro)-1.4'-pyrimidino]-pyrazines are obtained in the same way:

example can be used in the same way with similar success.

(b) Wool 100 parts of previously bleached wool flannel are washed for half an hour at in 2000 parts of a washing liquor containing 5 parts of an alkylaryl sulphonate of the marketed name Santomerse No. 1 and 0.05 part of 3-propylamino-S-ethylamino-pyrazine 2 carboxylic acid-propylamide-G carboxylic acid ethylamide. The wool is then rinsed and dried in the air. In this way wool of a considerably more white appearance is ob tained than when the Wool is washed without the addition of the brightening agent.

The 3-propylamino-S-methylamino pyrazine 2 carboxylic acid-propyla1nide-6-carboxylic acid methylamide and 3-methylamino-5-ethylamino-pyrazine-2 carboxylic acid methylamide-tS-carboxylic acid ethylamide described in the above example can be used in the same way with the same success instead of the brightening agent mentioned.

These unsymmetrical 3.S-bis-alkylamino-pyrazine-3.6-

icarboxylic acid alkylamides can be used according to the methods described in Examples 1 and 3 for the Elementary analysis, percent R1. alkyl R2. allylll M.P. deg. r

1 and R1 3 an 4 O cald 0 found H cald H found N eald N found C n-CaH-z 169-163. 5 53. 32 53. 36 5. 59 5. 57 23. 32 23. 24 CH; caHs- 253-254 50.60 50. e1 4. 85 4. 72

On saponifying these according to paragraph 2 of the above example, the corresponding unsymmetrical 1.3- bis-alkylamino-pyrazine 2.6 dicarboxylic acid-bis-alkylamides are obtained:

brightening of synthetic masses and synthetic fibres as well as of cosmetics.

EXAMPLE 3 3.5 bis methylamino pyrazine 2 carboxylic acid- Elementary analysis, percent 1. alkyl 2. alkyl M.P., deg. R1 and R R and R4 0 cald 0 found H eald H found N cald N found CH n-CaH- 136-137 54. 52 54. 64 7. 84 8.02 27. 25 26. 98 CH;- C Hy- 169-170 54. 41 51. 66 7. 19 7. 17 29. 98 29. 95

All these unsymmetrical 3.S-bis-alkylamino-pyrazine-2.6- dicarboxylic acid-bis-alkylamides have a strong to very strong vio1et-blue fluoroescence depending on their composition. Due to this property, they can be used for the brightening of natural and synthetic polypeptides as fol lows:

(a) Synthetic polypeptides phenylarnide-G-carboxylic acid methylamide of the formula:

31 .parts of 1.3-dimethyl-4-amino-uracil and 40 parts of LB-dimethyl 4 amino 5 nit-roso-ur'acil are refluxed while stirring for 3 hours in 200 parts of glacial acetic acid. The reaction mixture is cooled, the precipitate formed is filtered 01f under suction, washed well with Water and dried. 51 parts of 3.2:5.6-bis-[(1'.3'-dirnethyl- 2.4'-dioxo-1.2.3.4' tetrahydro) 1'.4 pyrimidino1- pyrazine are obtained in the form of white crystals which melt at 390 (the melting point depends on the heating time. This corresponds to a yield of 84% of the theoretical, calculated on the 1.3-dimethyl-4-arnino-uracil used. Recrystallised from acetic acid, an analytically pure preparation has the following elementary analysis:

Calculated for C H O N C=47.4%; H=4.17%; N=27.8%. Found: C=47.4%; H=3.95%; N=27.6%.

1 1 To saponify the 3.2:5.6-bis-[(1.3 dimethyl 2'.4- dioxo-1.2.3'.4'-tetrahydro)1.4'-pyrimidino] pyrazine, 152 parts are refluxed for 6 hours with a solution consisting of 200 parts of potassium hydroxide and 2400 parts of ethanol. 117 parts of 3.5-bis methylarnino 2- l 2 by steam distillation, the residue is filtered off under suction and washed well with water. Pale yellow crystals of 3.S-bis-methylamino-pyrazine-2 carboxylic acid phenylamide--carboxylic acid methylamide are obtained which melt at 195-197".

carboxy-pyrazine-6-carboxylic acid methylamide (MP. 5 Recrystallised from ethanol, an analytically pure prep- 214 decomposition dependent on the heating time) are aration melts at 198198.5 and has the following eleobtained. Recrystallised from ethanol, an analytically Inentary analysisf pure preparation has the following elementary analysis: Calculated for C H O N C=57.31%; H=5.77%; Calculated for C H O N +V2H O2 C=43.48%; H: 10 N=26.74%. Found: C:57.42%; H=6.01%; N: 5.68%; N=28.3%. Found: C=43.59%; H=5.50%; 26.86%. N=28.45%. Amidation of 3.S-bis-methylamino-Z-carboxy-pyrazine- To amidate the 3.5-bis-methylamino-2 carboxypyraz- 6-carboxylic acid methylamide in pyridine or in an aqueine-6-carboxylic acid methylamide 20 parts are mixed ous medium according to paragraph 3 of this example with 150 parts of thionyl chloride. The mixture is left 15 with the amines corresponding to R in the following to stand for 45 minutes and then the excess thionyl chlotable, produces the following compounds: ride is removed in the vacuum. The remaining crystal- N line acid chloride is then slowly added to a solution of OH NH C 10 parts of aniline and 400 parts of abs. pyridine, which 3- NH CH3 solution is cooled with a mixture of ice/sodium chloride 20 CH3NHO- -CR and stirred overnight. The pyridine is then removed H g No. R M.P., Colour of deg. fluorescence 1 NHz 290-292 Violet-blue.

2 NHCH2CH2OH 2l0-210.5 Do.

3 -NHCHz-CH2-CH2 218-219 Do.

4 NH-CH2CH3 197198.5 Do.

5 -NHCH;- 21s. 5-220 Blue-violet.

s NHCHzCHz- 76*78 Do.

1 NH@ 126. 5-12? Blue.

OCHa s NH-CHzOHgCH2CH 194-196 Violet-blue.

9 NHO 252-254 Blue.

10. NH-CH2-OH-CHZ 194-195.5 Violet-blue 11 NH-(CH2)1-CH3 121-121.5 Do.

OHPOHR 12 NHCH /OH 237-238 Blue-violet.

CH OH 13. -N 128-129 Violet. orra 14. NH-CH 188-190 Violet-blue.

H-C-CH 15 NH-O 0-H 223-224 Blue-violet.

N=CH 2 16"... NH?OH; 204-205 Vlolet-blue.

11.--- NH-OH3 211-2125 Blue-violet.

13..... NH@ 194-195 Do.

See footnote at end of table.

No. R M.P Colour 01' deg. fluorescence 36. HN 232-234 Blue-violet.

1 The melting points depend greatly on the heating time.

If, in the process according to paragraph 3 of the above example, ureas are reacted in pyridine with the 3.5-bismethylamino-2-carboxy-pyrazine-6-carboxy1ic acid meth- 1 The melting points depend greatly on the heating time.

On using corresponding amines of 1.3-dibenzyland 1.3-diethyl-4-amino-uracils and 1.3-dibenzyland 1.3-diethyl-4-amino-5-nitroso-uracils, the 3.2:5.6-bis-[(1.3'.dibenzyl 2'.4 dioxo-1.2'.3.4'-tetrahydro)-1.4'-pyrimidino]-pyrazines and 3.2 5.6-bisl '.3-diethyl-2.4'-dioxo- 1.2'.3.4'-tetrahydro)-1'.4-pyrimidino]-pyrazines are obtained in the same manner. On saponifying these according to paragraph 2 of this example, the corresponding 3.5- bissubstituted aminopyrazine-2-carboxylic acid-6-carboxylic acid benzylor ethylamides are obtained.

1:40) containing 0.01 parts of 3.S-bis-methylamino-pyrazine-2-carboxylic acid phenylamide-6-carboxylic acid methylamide and 0.2 part of formic acid. After rinsing and drying, the fabric treated has a much more white appearance in daylight than before treatment. I

(2) 50 parts of undyed nylon are washed at 70 for half an hour in a washing liquor (liquor ratio 1:20) containing 0.03 part of 3.5-bis-methylamino-pyrazine-Z-carboxylic acid- [3 '-methoxyphenylamide -6-carboxylic acid methylamide and 8 parts of dodecyl benzene sulphonate, and then rinsed and dried. The nylon so treated has a much more brilliant appearance in daylight than material washed without the addition of brightening agent. Instead of dodecyl benzene sulphonate, also other synthetic washing and cleansing agents such as, for example, fatty alcohol sulphates or olcoyl tauric acid alkali salts etc. can be used. 7

The following compounds described in the above tables can be used in the same manner with similar success instead of the brightening agents mentioned: Nos. 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 14, 15, 16, 19, 20, 21, 22, 23, 24, 25, 26, 27, 29, 30, 31, 33, 34, 36, 38, 39, 40 and 41.

(b) Wool (1) 25 parts of white woollen knitted goods are treated in a dyebath (liquor ratio 1:30) for half an hour at which contains 0.02 part of 3.5-bis-methylaminopyrazine-Z-carboxylic acid phenylamide-6-carboxylic acid 40 methylamide and 0.5 part of formic acid. The goods Elementary analysis in percent Substituent R1, R and Ra 1%.12,

0 cald 0 found H eald I-I found N cald N found OHi- 161-162 69. 3e 69. '30 5. 39 5.36 14. 98 15.06

-CzHs 174-175 51. 23 51. 32 6. 81 7. 02 24. 90 25. 08

By amidation in pyridine according to paragraph 3 of this example, the corresponding 3.5-bis-ethylor benzylaminopyrazine-Z-carboxylic acid ethylor benzylamide- 6-carboxylic acid amides are obtained, for example:

are then rinsed and dried. The Wool so treated is clearly more white in daylight than untreated wool.

(2) 50 parts of previously bleached wool flannel are treated for 1 hour at 50-55" in a dyebath (liquor ratio Elementary analysis in percent N o. Substituent X M.P., deg.

R1, R and R3 Ccald Ciound Hcald Hiound Ncald Niound 4o 01H. -NH-C 60.65 60. 77 6. 79 7.07 23.58 23.55

41 C 11 NH-O 108-109 56.9 66.6 6.7 6.7 26.6 26.6

t E HO CH 1:20) containing 3 parts of sodium hydrosulphite and 1 part of sodium pyrophosphate and also 0.05 part of 3.5- bis-methylamino-pyrazine-2-carb0xylic acid phenylarnideo-carboxylic acid methylamide. After rinsing and drying, the wool flannel has a considerably more White appear- (1) 10 parts of a, pale yellowish nylon f b i re ance than material treated without the addition of treated for 30 minutes at 70 in a dyebath (liquor ratio brightening agents.

17 The following compounds in the above tables can be used in the same manner with the same success: Nos.

22, 23, 24, 25, 27, 29, 30, 31, 39, 40 and 41.

(6) Pure silk parts of pale yellowish pure silk are Washed at 55 for 30 minutes in 200 parts of a washing liquor containing 0.5 part of an alkylaryl sulphonate of the mar-. keted name Santomerse No. 1 and 0.01 part of 3.5-bismethylamino-pyrazine-2-carboxylic acid phenylamide-6- carboxylic acid methylamide, and then rinsed and dried in the air. In this way, pure silk of considerably more white appearance is obtained than if it had been washed without the addition of the brightening agent named.

Also very beautiful effects are obtained if instead of the brightening agent used above, the following compounds mentioned in the tables are used: Nos. 1, 2, 3, 4, 5, 7, 11,12, 15, 27 and 31.

' (d) Acetate silk 10 parts of acetate silk' fabric are treated at 75 for 30 minutes in a bath (liquor ratio 1:30) containing 0.0025 part of 3.5-bis-methylaminopyrazine-Z-carboxylic acid phenylamide-6-carboxylic acid methylamide. After rinsing and drying, the fabric has a considerably more white appearance than before treatment.

The following compounds described in the above tables can be used in the same manner with similar success instead of the brightening agent mentioned: No. 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 14, 15, 16, 18, 19, 20, 21, 22, 23, 26, 27, 29, 31, 33, 35, 3'9, 40 and 41.

(e) Cellulose triacetate V 10 parts of cellulose triacetate silk fabric are treated for half an hour in a dyebath on a boiling water bath, the dyebath liquor ratio being 1:30 and containing 0.005 part of 3.5-bis-methylaminopyrazine-Z-carboxylic acid phenylamide-6-carboxylic acid methylamide. After rinsazine, produced for example as in Example 2, 57 parts of this compound are refluxed for 6 hours with a solution consisting of parts of potassium hydroxide and 500 parts of ethanol. The ethanol is distilled off, the reaction mixture acidified with diluted-hydrochloric acid and 43 parts of 3-methylamino-S-ethylamino-pyrazine-Z-carboxylic acid-fi-carboxylic acid ethylamide are isolated. The compound melts at 160-162 (the melting point depends on the heating time);

Recrystallized from methanol, an analytically pure preparation has the following elementary analysis:

Calculated for C11H117O3N5I C=49.43%; H=6.4l%; N=26.20%. Found: C=49.99%; H=6.49%; N: 26.27%. i i

To amidate the 3-m'ethylamino-3-ethylamino-pyrazine- 2-carboxylic acid-6-carboxylic acid ethylarnide, 20 parts of this compound are mixed with 100 parts of thionyl chloride. The mixture is left to stand for 45 minutes and then excess th-ionyl chloride is removed in the vacuum. The acid chloride which remains is then poured into a solution of 300 parts of concentrated aqueous ammonia and 100 parts of ethanol, which solutionhasbeen cooled with arnixture of ice and sodium chloride. is stirred overnight. The precipitate formed is filtered off under suction and washed well with water. 3-methylamino-S-ethylaminmpyrazine-2-carboxylic acid amide-6- carboxylic acid ethylamide is obtained in the form of pale yellow crystals which melt at 212-214".

Recrystallized from ethanol, an analytically pure preparation melting at 223 2334 has the following elementary analysis:

Calculated for C H O N C=49.61%; H=6.81;%;

The following 3-methylamino-5-ethylamino-pyrazine-2- carboxylic acid alkylamide-6-carboxylic acid ethylarnides for example are obtained in the same manner on amidation with other amines:

, Elementary analysis in percent Allyl 1%.?

0 cald 0 found I H cald l Hlound .Nl cald Ntound ing and drying, the fabric has a much morebrilliant appearance than before treatment.

. Instead of 3.S-bis-methylamino-pyrazine-2-carboxylic acid phenylamide-6-carboxylic acid methylamide,the.fol-

EXAMPLE 4 3-methylamino 5 ethylamino-pyrazine-2-carboxylic acid amido-6-carboxylic acid ethylamide of the formula:

Depending on their composition, all these 3-methylamino-5-ethylamino-2-carboxylic acid alkylamide-6-carboxylic acid ethylamides have a strong'to very strong violet-blue fluorescence. Because of this property they can be used for the brightening of natural. as well as synthetic polypeptide fibres. j

Wool treated in an acid bath according to paragraph (b) of Example 3. 0r,ini a neutral bath according to paragraph (b) of Example 2 has a considerably more white appearance than untreatedwool.

Nylon treated in an acid bath according to paragraph (a) of Example '3 has a much more white and luminous appearance than before treatment.

1 Also fibres made up from cellulose acylates can be beautifully brightened with these unsymmetrical pyrazine derivatives. For example, acetate silk fabric has a much more white appearance after treatment according to paragraph (d) of Example 3 than untreated fabric.

Such 3-methylamino5-ethylamino-Z-carboxylic acid alkylamide-6-carboxylic acid ethyl amides are also suit- 1 The Whole.

1% (a)v of Example 1, have a much more White appearance in daylight than such foils which contain no brightening agent. I

EXAMPLE 0.075 part of 3.S-bis-methylamino-pyrazine-2-carboxylic acid-phenylamide-6-carboxylic acid methylamide are worked into 100 parts of soap powder consisting of the sodium salt of fatty acids with 5% water content. Nylon fabric Washed at 40 in a washing liquor (liquor ratio 1:30) containing 5 parts per litre of the above soap powder described above, has a much more brilliant appearance.

' If, in the above washing agent, 0.09 part of 3.5-bismethylamino-pyrazine-2.6-dicarboxylic acid methylamide are used instead of the pyrazine named, then the treated fibres also have a beautiful white appearance. If an even stronger brightening effect on acetate silk is required, then 1 to 2 parts of the brightening agent named can be used.

EXAMPLE 6 washing agent, 0.2 part of 3.S-bis-methylamino-pyrazine- 2.6-dicarboxylic acid methylamide or 0.2 part of 3-propylamino5-methylamino-pyrazine-2-carboxylic acid propylamide-G-carboxylic acid methylamide or 0.15 part of 3- ethylamino-5-methylamine-pyrazine-2.6-dicarboxylic acid ethylamide or 0.3 part of 3-propy1amino-5-ethylaminopyrazine-Z-carboxylic acid propylamide-6-carboxylic acid ethylamide or 0.2 part of 3-ethylamino-5-methylamino V pyrazine-Z-carboxylic acid ethylamide-6-carboxylic acid benzylamide are used, then similar effects are obtained ontreating the fibres above mentioned. 1

Instead of the anion active Washing agent described,

7 also those consisting of salts of sulphonic acid esters of ethoxylated fatty alcohols or salts of sulphonic acid esters of alkonal amides of fatty acids can be used.

EXAMPLE 7 0.05 part of 3.S-bis-methylamino-pyrazine-Z-carboxylic acid phenylamide-6-carboxylic acid methylamide are worked into 100 parts of washing agent of the composition: 20% dodecyl benzene sulphonate, 15% sodium lauryl sulphonate, 2% carboxymethyl cellulose, 15% tetrapyrophosphate, 20% tripolyphosphate, 22% sodium sulphate and 6% Water.

If nylon or acetate silk is washed at 60 in a washing liquor containing 6 parts per litre of the washing agent described, then the fabric has a brilliant appearance.

If, in the above washing agent instead of the pyrazine mentioned, 0.12 part of 3.5-bis-ethylamino-pyrazine-Z.6- dicarboxylic acid methylamide are used, then the fibres mentioned also have a beautiful appearance.

If the washing agent contains 0.15 part of 3.5-bis-methyIaminO-pyIa ine-Z-carboxylic acid pyridylamide-6-carboxylic acid methyl amide, then wool flannel or acetate silk washed therein has a beautiful white appearance.

. EXAMPLE 8 0.2 part of 3.5-bis-methylarnino-pyrazine-2.6-dicarbox- 'ylic acid methylamide are incorporated into 100 parts of washing agent consisting of 45% soap, 5% Water glass, 10% pyrophosphate, sodium carbonate, 3% magnesium meta silicate, 7% perborate and 15% Water.

20 Nylon and acetate silk fabric which are washed at 70 in a washing liquor (liquor ratio 1:30) containing 8 parts per litre of the above washing agent have a much more white appearance than when washed without the addition of the brightening agent.

If in the above washing agent, instead of the brightening agent named, 0.06 part of 3.5-bis-methylamino-pyrazine-Z-carboxylic acid pyridylamide-6-carboxylic acid methylamide or 0.04 part of 3.5-bis-methylamino-pyrazine-2- carboxylic acid phenylamide-6-carboxylic acid methylamide, are used, then similar effects on the above mentioned fibres are obtained.

EXAMPLE 9 0.1 part of 3.5-bis-ethy1amino-pyrazine-2.6-dicarboxylic acid ethylamide are incorporated into 100 parts of washing agent of the compositon: 12% dodecyl benzene sulphonate, 10% sodium lauryl sulphate, 5% water glass, 2% carboxymethyl cellulose, 15% tripolyphosphate, 20% pyrophosphate, 10% sodium carbonate, 20% sodium sulphate and 6% water.

Nylon fabric which is washed at 70 in a washing liquor (liquor ratio 1:30) containing 8 parts per litre of the Washing agent described above, has a brilliant appearance.

If, in the above washing agent, instead of the pyrazine mentioned, 0.08 part of 3.5-bis-methylamino-pyrazine-Z.6- dicarboxylic acid methylamide or 0.005 part of 3.5-bismethylamino-pyrazine-2-carboxylic acid phenylamide-6- carboxylic acid methylamide are used, then a brightening eifect isalso obtained.

EXAMPLE 10 boxylic acid ethylamide instead of the pyrazine named,

'also has a-beautiful white appearance.

Also a washing agent consisting of the condensation product of oleic acid and taurine can be used instead of that described.

EXAMPLE 11 '0.075 part of 3-ethylamino-5-methylamino-pyrazine 2.6dicarboxylic acid ethylamide are incorporated into parts of washing agent consisting of 25% of a sulphonated condensation product of p-me'thoxyphenyl diguanide and oleic acid (1-p-methoxyphenyl-2-imino-4- amino-6-oleyl-1.3.S-triazine sulphonic acid), 70% sodium sulphate and 5% Water.

Nylon fabric Washed at 50 in a washing liquor (liquor ratio 1:30) which contains 5 parts per litre of the Washing 3.ibis-methylamino-pyrazine-2-carboxylic acid phenylamide-6-carboxylic acid ethylamide are used instead of the pyrazine mentioned.

- What we claim is:

1. A composition of matter of improved appearance in' daylight consisting of a cosmetic fatty cream and from 0.001 to 0.5% by Weight of a 3.5-diamino-pyrazine-2.'6- dicarboxylic acid amide of the formula:

wherein R R and R each represents a member selected from the group consisting of lower alkyl and phenyl substituted methyl and X represents a member selected from the group consisting of primary amino, secondary amino, tertiary amino and ureido.

2. A composition of matter of improved appearance in daylight consisting of a cosmetic fatty cream and from 0.001 to 0.5% by weight of 3.S-bis-methylarninopyrazine- 2.6-dicarboxylic acid-bis-methylamide.

3. A composition of matter of improved appearance in daylight consisting of a cosmetic fatty cream and 'from 0.001 to 0.5% by weight of 3.5bis-ethylaminopyrazine- 2:6-dicarboxylic acid-bis-ethylamide.

4. A composition of matter of improved appearance in daylight consisting of a cosmetic fatty cream and from 0.001 to 0.5% by Weight of 3.Sabis-ethylaminopyrazine- 2.6-dicarboxy1ic acid-bis-propylamide.

5. A composition of matter of improved appearance in daylight consisting of a cosmetic fatty cream and from 0.001 to 0.5% by Weight of 3.S bis-propylarninopyrazine- 2.6-dicarboxylic acid-bis-ethylamide.

6. A composition of matter of improved appearance in daylight consisting of a cosmetic fatty cream and from 0.001 to 0.5 by Weight of 3.5-bis-propy1aminopyrazine- 2.6-dicarboxylic acid-bis-propylamide.

References Cited by the Examiner UNITED STATES PATENTS 1/52 Timmi-s 260--25l.5

OTHER REFERENCES JULIAN S. LEVITI, Primary Examiner. 

1. A COMPOSITION OF MATTER OF IMPROVED APPEARANCE IN DAYLIGHT CONSISTING OF A COSMETIC FATTY CREAM AND FROM 0.001 TO 0.5% BY WEIGHT OF A 3.5-DIAMINO-PYRAZINE 2.6DICARBOXYLIC ACID AMIDE OF THE FORMULA 